Core-Shell Structured Porous Calcium Phosphate Bioceramic Spheres for Enhanced Bone Regeneration

Bone regeneration remains a significant challenge in clinical settings due to the need for effective osteogenesis. Calcium phosphate (CaP) bioceramics, such as hydroxyapatite (HA) and biphasic calcium phosphates (BCPs), are widely used for bone defect repair because of their osteoinductive and biodegradable properties. While these materials have shown promise, their performance can be limited by structural and functional constraints. Prior research has shown that the physical and chemical properties of CaP materials influence their integration with surrounding tissues and their ability to support new bone formation. However, no prior work had resolved how core-shell structured CaP granules might improve these outcomes. This gap motivated the development of novel CaP bioceramic designs with enhanced structural and biological features. The need for better control over porosity, mechanical stability, and cellular interactions has driven recent innovations in bioceramic fabrication. Understanding how material architecture affects bone regeneration is essential for improving clinical outcomes. This study addresses the need for more effective bone graft materials by introducing a new structural design approach.

This study aimed to design and fabricate core-shell structured porous calcium phosphate (CaP) bioceramic granules to improve bone regeneration. The specific problem addressed was the need for better control over the physical and biological properties of bone graft materials. The motivation stemmed from the limitations of conventional CaP materials in promoting new bone growth and vascularization. The researchers proposed that a core-shell structure might enhance the osteogenic and anti-osteoclastic properties of CaP granules. By combining calcium alginate gel molding with a hydrogen peroxide foaming process, the team aimed to create spherical granules with controlled porosity and structure. The study sought to evaluate the in vitro and in vivo performance of two types of core-shell granules: BCP@HA and HA@BCP. The goal was to determine whether these structures could support bone marrow mesenchymal stem cell proliferation and suppress osteoclast formation. The ultimate objective was to develop a more effective bone graft material for clinical use.

The researchers used calcium alginate gel molding combined with a hydrogen peroxide foaming technique to fabricate spherical bioceramic granules. This method allowed for the creation of core-shell structures with defined compositions. Two types of granules were produced: BCP@HA and HA@BCP, where the core and shell phases were composed of different CaP materials. The granules were characterized for their shape, porosity, and micropore size distribution. In vitro experiments involved co-culturing the granules with bone marrow mesenchymal stem cells and RAW264.7 cells to assess proliferation, osteogenic differentiation, and osteoclast formation. In vivo testing was conducted using a critical-sized femoral bone defect model in animals. The implants were analyzed after 12 weeks for bone volume fraction, bone mineral density, and vascularization. Histological and 3D microvascular perfusion angiography techniques were used to evaluate tissue integration and blood vessel formation. The study focused on comparing the performance of the two core-shell structures against conventional CaP materials.

The HA@BCP granules showed a higher bone volume fraction and bone mineral density compared to BCP@HA, pure HA, or BCP after 12 weeks of in vivo implantation. Histological analysis revealed that new bone tissue in the HA@BCP group invaded from the surface to the interior of the granules, with most of the bioceramic phase replaced by new bone. The HA@BCP group also demonstrated a higher vessel volume fraction, indicating better vascularization in the defect region. In vitro, HA@BCP granules promoted the proliferation and osteogenic ability of bone marrow mesenchymal stem cells. These granules also inhibited the differentiation of RAW264.7 cells into osteoclasts, suggesting an anti-resorptive effect. The porosity of the granules ranged between 65-70%, with micropores between 150 and 450 μm, which is considered favorable for bone ingrowth. The spherical shape and porous structure were achieved through the calcium alginate gel molding and H2O2 foaming process. The results suggest that the HA@BCP core-shell structure enhances both osteogenic and anti-osteoclastic properties compared to other configurations.

The current study demonstrated that core-shell structured HA@BCP bioceramic granules could be a promising candidate for bone defect repair. The HA@BCP configuration outperformed BCP@HA, pure HA, and BCP in terms of bone volume fraction, bone mineral density, and vascularization. The researchers propose that the HA@BCP structure supports new bone formation by promoting stem cell proliferation and osteogenesis while inhibiting osteoclast differentiation. The in vitro and in vivo results suggest that the HA@BCP granules have superior biological performance compared to other CaP structures. The study supports the idea that the core-shell architecture enhances the integration of bioceramics with surrounding tissues. The findings suggest that this design could improve clinical outcomes in bone regeneration. The researchers propose that the HA@BCP structure may be more effective in supporting long-term bone repair and integration. The study highlights the potential of core-shell structured CaP granules as a next-generation bone graft material.